What is the differential diagnosis (ddx) and management approach for a patient presenting with symptoms suggestive of gout?

Differential Diagnosis of Gout

Primary Differential Diagnoses to Exclude

The most critical differential diagnosis to rule out when evaluating suspected gout is septic arthritis, as gout and infection can coexist and clinical algorithms cannot reliably distinguish between them. 1

Key Conditions in the Differential:

• Septic arthritis - Joint aspiration with Gram stain and culture is mandatory when infection is suspected, as this is the only reliable method to exclude bacterial infection 1, 2

• Calcium pyrophosphate deposition disease (CPPD/pseudogout) - Among patients with false-positive gout diagnoses using clinical criteria, 50% had calcium pyrophosphate crystals on synovial fluid analysis 1

• Rheumatoid arthritis - Can present with polyarticular inflammation; 3% of rheumatoid arthritis patients fulfilled clinical gout diagnostic criteria in validation studies 1

• Osteoarthritis with acute inflammation - 3% of osteoarthritis patients met clinical gout criteria in validation studies 1

• Other crystal arthropathies - Including basic calcium phosphate deposition disease

Diagnostic Approach: Three-Step Algorithm

Step 1: Synovial Fluid Analysis (Gold Standard)

Joint aspiration with polarized light microscopy for monosodium urate (MSU) crystals is the definitive diagnostic test and should be performed in all cases of undiagnosed inflammatory arthritis. 1, 2, 3

• MSU crystals appear as needle-shaped, negatively birefringent crystals under polarizing microscopy 4
• Sensitivity ranges from 63-78% and specificity from 93-100% when performed by experienced examiners 2
• Critical caveat: Even when MSU crystals are identified, Gram stain and culture must still be performed as gout and septic arthritis can coexist 4
• Complications are rare: severe complications occur in 0.1% of cases, mild complications (mostly pain) in 1.4% 2

Step 2: Clinical Diagnosis (When Aspiration Not Feasible)

If joint aspiration is not possible, use the 2015 ACR/EULAR classification criteria, which require a score ≥8 points for diagnosis (sensitivity 92%, specificity 89% with imaging; 85% sensitivity, 78% specificity without imaging). 3

High-Value Clinical Features:

• Podagra (first metatarsophalangeal joint involvement) - Most specific clinical finding 1
• Presence of tophi - Odds ratio 7.29 for gout diagnosis 3
• Maximal joint inflammation within 24 hours - Highly suggestive 3
• Erythema over the affected joint 3
• Resolution of pain within 2 weeks - Odds ratio 3.58 3
• Male sex and cardiovascular comorbidities 3

Important Limitations of Clinical Diagnosis:

• Hyperuricemia alone is NOT diagnostic - Many hyperuricemic patients never develop gout, and acute gout can occur with normal serum uric acid levels during an attack 1, 4
• Clinical algorithms (Janssens rule, CGD criteria) have sensitivities and specificities above 80% but may miss alternative diagnoses like septic arthritis 2
• For early gout (<2 years duration), the Janssens diagnostic rule shows better sensitivity (73-88%) with specificity of 75-86% 1

Step 3: Imaging (When Clinical Diagnosis Uncertain)

When clinical diagnosis is uncertain and crystal identification is not possible, imaging should be used to search for MSU crystal deposition. 1, 2

Imaging Modalities in Order of Diagnostic Accuracy:

• Dual-energy CT (DECT) - Most accurate non-invasive test with sensitivity 85-100% and specificity 83-92%, but less sensitive for early gout 2, 3

• Ultrasound - Highly specific for detecting the "double contour sign" on cartilaginous surfaces (pooled sensitivity 74%, specificity 88%); can identify subclinical tophi not evident on examination 1, 2, 3

• Plain radiographs - Limited value for acute gout diagnosis; useful for detecting chronic changes and excluding alternative diagnoses 1

Essential Laboratory Evaluation

• Serum uric acid - Essential for management but insufficient for diagnosis; normal levels during acute attacks do not exclude gout 1, 4

• Renal function tests (creatinine, BUN) - Important for medication selection and dosing 4

• Complete blood count - To assess for infection and other inflammatory conditions

• Inflammatory markers (ESR, CRP) - Elevated in both gout and septic arthritis, cannot distinguish between them

Risk Factors to Assess

Systematically evaluate for risk factors and comorbidities in all patients with suspected gout: 1

• Chronic kidney disease
• Obesity
• Medications: diuretics (thiazide, loop), low-dose aspirin, cyclosporine, tacrolimus 1
• Excessive alcohol consumption (particularly beer and spirits) 1
• High intake of meat, shellfish, and high-fructose beverages 1
• Associated comorbidities: hypertension, ischemic heart disease, heart failure, diabetes, dyslipidemia 1

Common Diagnostic Pitfalls to Avoid

• Failing to aspirate when septic arthritis is possible - This is the most dangerous error; delayed diagnosis of septic arthritis leads to longer hospitalizations and worse outcomes 2

• Relying solely on serum uric acid levels - Up to 40% of patients have normal uric acid during acute attacks 4

• Assuming atypical presentations are not gout - Polyarticular gout and unusual locations can occur, particularly in chronic disease 5

• Not performing Gram stain/culture when MSU crystals are found - Coexistent infection must be excluded 4

• Using classification criteria as diagnostic criteria - The ACR/EULAR criteria were designed for research enrollment, not individual patient diagnosis, though they perform well in clinical practice 1, 3